Glutamate is the major excitatory neurotransmitter in the brain. The amount of glutamate transported into vesicles could change the strength of a synapse. This proposal aims to 1) distinguish between competing models of vesicle filling by asking whether glutamate transport is necessary for increases in vesicle size, 2) determine the number of glutamate transporters on a vesicle, and 3) investigate homeostatic mechanisms that attenuate the excitatory effects of excess glutamate release. Understanding the consequences of reduced and increased vesicular glutamate transporter expression and their effects on synapse strength will provide insight into the biology of glutamatergic synaptic vesicles, excess glutamate release and excitotoxicity, and homeostatic mechanisms that regulate glutamate release. [unreadable] [unreadable]